The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)
Primary Purpose
Covid19
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ivermectin 0.6mg/kg/day
Ivermectin 1.0mg/kg/day
Placebo
Hydroxychloroquine
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID-19, SARS-CoV-2, Covid19, Ivermectin
Eligibility Criteria
Inclusion Criteria:
- Laboratory or clinically confirmed positive SARS-CoV-2 rtPCR test (AndroCoV Clinical Scoring for COVID-19 Diagnosis1) within 7 days prior to randomization
- ≥18 years old
- Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
- Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 1 to 3
- Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures
- Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study
Exclusion Criteria:
- Subject enrolled in a study to investigate a treatment for COVID-19
- Require oxygen use, hospitalization or mechanical ventilation
- Tachycardia (HR > 150 bpm) or hypotension (BP < 90/60 mmHg)
- Patients who are allergic to the investigational product or similar drugs (or any excipients);
- Subjects with QTcF > 450 ms
- Subjects with uncontrolled medical conditions that could compromise participation in the study - uncontrolled hypertension (BP > 220/120 mmHg), uncontrolled hypothyroidism (TSH > 10 iU/L), uncontrolled diabetes mellitus (HbA1c > 12%)
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
- Estimated glomerular filtration rate (eGFR) < 30 ml/min or requiring dialysis
- Subject (or legally authorized representative) not willing or unable to provide informed consent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Ivermectin 0.6mg/kg/day
Ivermectin 1.0mg/kg/day
Placebo
Arm Description
Outcomes
Primary Outcome Measures
World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]
Secondary Outcome Measures
World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] [Time Frame: Day 7]
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death]
Time-to-recovery
Recovery is defined as the first day on which the subject satisfies category one from the COVID ordinal scale (defined in Section 5.1): (1) Not hospitalized, no limitations on activities. [Parameter: Number of days until achieve Category 1 of the World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death]
Viral load
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by viral load measured by rtPCR-SARS-CoV-2 (CTs)
Positivity rate of rtPCR-SARS-CoV-2 (qualitative analysis)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by viral load measured by positivity rate (% of positive, detected rtSARS-CoV-2)
Duration of fatigue
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of fatigue (days)
Duration of anosmia
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of anosmia (days)
Overall duration of clinical manifestations
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of overall symptoms (days)
Proportion of subjects needing additional drugs or interventions
Defined as the number of subjects who have required additional drugs (glucocorticoids, anticoagulants, etc) or interventions allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing additional drugs or interventions in each arm.
Proportion of subjects needing oxygen use
Defined as the number of subjects who have required oxygen use allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing oxygen use in each arm.
Proportion of subjects needing high-flow oxygen therapy or non-invasive ventilation
Defined as the number of subjects who have required high-flow oxygen use or non-invasive mechanical ventilation allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing high-flow oxygen use or non-invasive mechanical ventilation in each arm.
Proportion of hospitalizations
Defined as the number of hospitalizations in each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of hospitalizations in each arm.
Proportion of mechanical ventilation use
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of mechanical ventilation use in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of pressors use
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects needing use of pressors in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of deaths
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects who have died in each arm divided by the numbers of subjects randomized to the treatment arm (%).
Proportion of post-COVID mental symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID mental symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID mental symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID physical symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID physical symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID physical symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID overall symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID overall symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Proportion of post-COVID overall symptoms
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Duration of new oxygen use
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of new oxygen use measured in days among subjects that did not require oxygen upon randomization and required oxygen use after the beginning of treatment, in each arm (days)
Duration of hospitalization
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of hospitalization measured in days among subjects that required hospitalization, in each arm (days)
Duration of mechanical ventilation
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of mechanical ventilation measured in days among subjects that required mechanical ventilation, in each arm (days)
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Proportion of increased d-dimer (defined as d-dimer > 500 mg/dL)
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased d-dimer protein (usCRP) at Day 7, divided by the number of subjects randomized to that specific arm (%).
Disease duration
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of symptoms, complications, or any other COVID-related clinical or biochemical sign of disease
Change in viral load from baseline to Day 5
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by change in viral load from baseline to Day 5 measured by rtPCR-SARS-CoV-2 (CTs)
Full Information
NCT ID
NCT04712279
First Posted
January 13, 2021
Last Updated
January 14, 2021
Sponsor
Corpometria Institute
1. Study Identification
Unique Protocol Identification Number
NCT04712279
Brief Title
The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)
Official Title
High-Dose Ivermectin for Mild-to-Moderate COVID-19 - The (HD)IVACOV Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 25, 2021 (Anticipated)
Primary Completion Date
March 21, 2021 (Anticipated)
Study Completion Date
April 20, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Corpometria Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Ivermectin, a classical antiparasitic and anti-scabies agent, has demonstrated antiviral activity for a variety of viruses including chikungunya virus, zyka virus and dengue virus and was tested as a potentially effective for COVID-19.
Although ivermectin demonstrated potent in vitro action by reducing viral load by 5000x after 48 hours of incubation, simultaneous pharmacokinetics simulations suggested that the minimum effective concentrations would be unfeasible to be reached within safety range (EC-50 = 2 Micromol).
However, despite the theoretical unfeasible concentrations to be achieved, preliminary observational yet well-structured studies followed by randomized clinical trials (RCTs) demonstrated ivermectin efficacy when combined with hydroxychloroquine, doxycycline or azithromycin, which was corroborated by a recent systematic review and metanalysis. In common, a dose-response effect for effectiveness was observed, and no adverse effects was reported at any dose between 0.2mg/kg/day and 1.0mg/kg/day.
Based on the scientific rationale combined with the preliminary evidence, ivermectin has sufficient evidence to be tested in higher doses in a RCT for COVID-19. The investigators propose to test ivermectin at high doses as a treatment for patients recently diagnosed with COVID-19, aiming to explore the possible protective role of high-dose ivermectin in SARS-CoV-2 infection in terms of reduction of clinic and virologic disease duration, and prevention of oxygen use, hospitalization, mechanical ventilation, death, and post-COVID persisting symptoms.
Detailed Description
Overall
COVID-19 is a multisystemic disease caused by SARS-CoV-2 that has become a pandemic largely due to a combination of favorable transmission and infection characteristics for its spread, including prolonged preclinical or also asymptomatic yet transmitting period, relatively highly resistant to mechanical and physical barriers and prolonged survival in the air, and transmission patterns not yet fully elucidated.
While vaccines are not widely available, the number of new cases should not decrease dramatically, unfortunately, since a large percentage of the population has not been infected by the SARS-CoV-2 yet, reinfection becomes increasingly plausible with mutations in the virus, and virus contention policies failed to be 100% effective.
Considering potential antiviral approaches for COVID-19, their effectiveness only make sense if tested and given early in the disease, during viral dissemination. The learning that oseltamivir is only effective for Influenza A in the first three days of disease finds strong plausibility, and reinforces the expected lack of effectiveness of any drug with in vitro or preliminary antiviral activity reported when tested in hospitalized or non-mild patients, once COVID-19 presents tend to present mild symptoms during the viral dissemination stage.
An actual early detection of COVID-19, i.e., before its progression to further inflammatory stages, is challenging, once the earliest symptoms tend to be unspecific, mild, and hardly attributable to COVID-19. By suspecting of COVID-19 in the presence of any symptom, specific to COVID-19 or not, sensitivity was met to be above 90% while specificity was also relatively high (above 50%). In addition, time-to-treat, rather than which drug to choose, could better determine the effectiveness of a specific approach.
Ivermectin: potential antiviral activity for COVID-19
Among drugs potentially effective for COVID-19, despite the classical antiparasitic and anti-scabies use, ivermectin has demonstrated antiviral activity for a variety of viruses by inhibiting and reducing the viral shedding duration, including chikungunya and other alphaviruses, zyka virus, dengue virus and other simple-strain RNA viruses.
In the search for drugs with anti-SARS-CoV-2 activity, considering its effects on other viruses, ivermectin was tested in a Vero-hSLAM cell model and demonstrated potent in vitro action, by reducing viral load by 5000x after 48 hours of incubation. However, after initial promising results, simultaneous pharmacokinetics simulations suggested that the minimum effective concentrations would be unfeasible to be reached within safety range (EC-50 = 2 Micromol).
Although the theoretical minimum concentration required for antiviral action was apparently at least 17 times higher than the lethal dose and up to 10,000 times the usually prescribed doses for humans ( IC50 of 2.2 - 2.8 µM for monkeys), which would reduce the chances of ivermectin efficacy for COVID-19, preliminary observational yet well-structured studies demonstrated substantial synergistic action of ivermectin when added to "standard of care", usually hydroxychloroquine with or without macrolides. In a specific study, the use of ivermectin, even in low doses, reduced by 40% the absolute risk of death among patients more severely affected by COVID-19.
Some randomized clinical trials (RCTs) demonstrated efficacy of ivermectin when combined with hydroxychloroquine, doxycycline or azithromycin, in both mildly (and presumedly early) and more severely affected subjects with COVID-19. Demonstrated benefits included lower disease progression and reduced COVID-related mortality.
In comparative analyses, combinations between ivermectin and azithromycin, doxycycline or hydroxychloroquine demonstrated superiority compared to combinations between hydroxychloroquine and azithromycin or hydroxychloroquine alone.
The exact mechanisms of action remain nuclear. At least one study employing higher doses (0.6mg/kg/day) demonstrated in vivo antiviral activity, but only when maximum concentration reached serum levels above 160 ng/ml, which only occurred in 45% of subjects, even at higher doses. The antiviral mechanisms include modification in the ACE-2 glycation patterns, inhibition of the viral Helicase (NSP13) and disruption of the alpha-importin heterodimer.
In a recent systematic review and metanalysis, a dose-response correlation has also been observed in terms of endpoints, reinforcing the role of ivermectin as actins as an anti-SARS-CoV-2 action drug. However, even in lower doses ivermectin was able to demonstrate clinical benefits, allowing the hypothesis that ivermectin also exerts anti-inflammatory effects, which could include the blockage of STAT-1 migration to the nucleus, and could justify its use even at later stages of the disease.
Collectively, higher yet safe ivermectin doses find stronger plausibility and preliminary evidence to be tested in RCTs. In addition, approaches to increase ivermectin absorption and bioavailability should be encouraged.
Based on the scientific rationale combined with preliminary evidence, ivermectin has sufficient evidence to be tested at higher doses in a RCT for COVID-19. The investigators propose to test ivermectin at high doses as a treatment for patients recently diagnosed with COVID-19. This study is intended to explore the possible protective role of high-dose ivermectin in SARS-CoV-2 infection in terms of reduction of clinic and virologic disease duration, and prevention of oxygen use, hospitalization, mechanical ventilation, death, and post-COVID persisting symptoms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID-19, SARS-CoV-2, Covid19, Ivermectin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
294 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ivermectin 0.6mg/kg/day
Arm Type
Active Comparator
Arm Title
Ivermectin 1.0mg/kg/day
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ivermectin 0.6mg/kg/day
Intervention Description
Use of ivermectin 0.6m/kg/day q.d.for 05 days
Intervention Type
Drug
Intervention Name(s)
Ivermectin 1.0mg/kg/day
Intervention Description
Ivermectin 1.0mg/kg/day q.d. for 05 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo q.d.for 05 days
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine 200mg/day q.d. for 05 days
Primary Outcome Measure Information:
Title
World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] [Time Frame: Day 7]
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death]
Time Frame
Day 7
Title
Time-to-recovery
Description
Recovery is defined as the first day on which the subject satisfies category one from the COVID ordinal scale (defined in Section 5.1): (1) Not hospitalized, no limitations on activities. [Parameter: Number of days until achieve Category 1 of the World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death]
Time Frame
Day 28
Title
Viral load
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by viral load measured by rtPCR-SARS-CoV-2 (CTs)
Time Frame
Day 5
Title
Positivity rate of rtPCR-SARS-CoV-2 (qualitative analysis)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by viral load measured by positivity rate (% of positive, detected rtSARS-CoV-2)
Time Frame
Day 5
Title
Duration of fatigue
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of fatigue (days)
Time Frame
Day 14
Title
Duration of anosmia
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of anosmia (days)
Time Frame
Day 14
Title
Overall duration of clinical manifestations
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of overall symptoms (days)
Time Frame
Day 14
Title
Proportion of subjects needing additional drugs or interventions
Description
Defined as the number of subjects who have required additional drugs (glucocorticoids, anticoagulants, etc) or interventions allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing additional drugs or interventions in each arm.
Time Frame
Day 28
Title
Proportion of subjects needing oxygen use
Description
Defined as the number of subjects who have required oxygen use allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing oxygen use in each arm.
Time Frame
Day 28
Title
Proportion of subjects needing high-flow oxygen therapy or non-invasive ventilation
Description
Defined as the number of subjects who have required high-flow oxygen use or non-invasive mechanical ventilation allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of subjects needing high-flow oxygen use or non-invasive mechanical ventilation in each arm.
Time Frame
Day 28
Title
Proportion of hospitalizations
Description
Defined as the number of hospitalizations in each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the proportion of hospitalizations in each arm.
Time Frame
Day 28
Title
Proportion of mechanical ventilation use
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of mechanical ventilation use in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 28
Title
Proportion of pressors use
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects needing use of pressors in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 28
Title
Proportion of deaths
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects who have died in each arm divided by the numbers of subjects randomized to the treatment arm (%).
Time Frame
Day 28
Title
Proportion of post-COVID mental symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 30
Title
Proportion of post-COVID mental symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 60
Title
Proportion of post-COVID mental symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 90
Title
Proportion of post-COVID physical symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 30
Title
Proportion of post-COVID physical symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 60
Title
Proportion of post-COVID physical symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 90
Title
Proportion of post-COVID overall symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 30
Title
Proportion of post-COVID overall symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 60
Title
Proportion of post-COVID overall symptoms
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 90
Title
Duration of new oxygen use
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of new oxygen use measured in days among subjects that did not require oxygen upon randomization and required oxygen use after the beginning of treatment, in each arm (days)
Time Frame
Day 28
Title
Duration of hospitalization
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of hospitalization measured in days among subjects that required hospitalization, in each arm (days)
Time Frame
Day 28
Title
Duration of mechanical ventilation
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the duration of mechanical ventilation measured in days among subjects that required mechanical ventilation, in each arm (days)
Time Frame
Day 28
Title
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 1
Title
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 3
Title
Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Days 1, 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 7
Title
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 1
Title
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 3
Title
Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 7
Title
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 1
Title
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 3
Title
Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to Day 1)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Days 2, 3 and 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 7
Title
Proportion of increased d-dimer (defined as d-dimer > 500 mg/dL)
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by the number of subjects presenting increased d-dimer protein (usCRP) at Day 7, divided by the number of subjects randomized to that specific arm (%).
Time Frame
Day 7
Title
Disease duration
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by duration of symptoms, complications, or any other COVID-related clinical or biochemical sign of disease
Time Frame
Day 14
Title
Change in viral load from baseline to Day 5
Description
Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by change in viral load from baseline to Day 5 measured by rtPCR-SARS-CoV-2 (CTs)
Time Frame
Day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Laboratory or clinically confirmed positive SARS-CoV-2 rtPCR test (AndroCoV Clinical Scoring for COVID-19 Diagnosis1) within 7 days prior to randomization
≥18 years old
Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 1 to 3
Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures
Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study
Exclusion Criteria:
Subject enrolled in a study to investigate a treatment for COVID-19
Require oxygen use, hospitalization or mechanical ventilation
Tachycardia (HR > 150 bpm) or hypotension (BP < 90/60 mmHg)
Patients who are allergic to the investigational product or similar drugs (or any excipients);
Subjects with QTcF > 450 ms
Subjects with uncontrolled medical conditions that could compromise participation in the study - uncontrolled hypertension (BP > 220/120 mmHg), uncontrolled hypothyroidism (TSH > 10 iU/L), uncontrolled diabetes mellitus (HbA1c > 12%)
Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
Estimated glomerular filtration rate (eGFR) < 30 ml/min or requiring dialysis
Subject (or legally authorized representative) not willing or unable to provide informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flavio A Cadegiani, MD, PhD
Phone
+55 61 99650.6111
Email
flavio.cadegiani@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ricardo A Zimerman, MD
Organizational Affiliation
Corpometria Institute
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Flavio A Cadegiani, MD, PhD
Organizational Affiliation
Corpometria Institute; Applied Biology
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
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Learn more about this trial
The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)
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